This project is directed at delineating the pathogenic mechanisms of HIV infection and the role of immune activation in the propagation of disease and destruction of the immune system. We have demonstrated that, after tetanus toxoid booster inoculation, HIV-1 infected patients had transient increases in plasma viremia after immunization, increases in proviral burden, and increased viral load within lymph nodes. HIV was more easily isolated from PBMCs from the majority of patients after immunization than before immunization. We also demonstrated an enhanced susceptibility of normal PBMCs to HIV infection in vitro after tetanus immunization. Tetanus immunization was associated with dramatic and generally reversible shifts in the composition of plasma viral quasi-species. The plasma viral bursts in most cases reflected a non-specific increase in viral replication, secondary to an expanded pool of susceptible CD4+ T cells. In one patient, however, immunization favored the expansion of M-tropic(NSI) over dual tropic(SI) viruses. In one of three patients the data suggested that immune activation resulted in the appearance in plasma of virus induced from latently infected cells. These findings demonstrate how antigenic stimulation influences the dynamics of HIV replication including the relative expression of different viral variants.
